SARS-CoV-2 receptor is co-expressed with elements of the kinin-kallikrein, renin-angiotensin and coagulation systems in alveolar cells

Sci Rep. 2020 Nov 11;10(1):19522. doi: 10.1038/s41598-020-76488-2.

Abstract

SARS-CoV-2, the pathogenic agent of COVID-19, employs angiotensin converting enzyme-2 (ACE2) as its cell entry receptor. Clinical data reveal that in severe COVID-19, SARS-CoV-2 infects the lung, leading to a frequently lethal triad of respiratory insufficiency, acute cardiovascular failure, and coagulopathy. Physiologically, ACE2 plays a role in the regulation of three systems that could potentially be involved in the pathogenesis of severe COVID-19: the kinin-kallikrein system, resulting in acute lung inflammatory edema; the renin-angiotensin system, promoting cardiovascular instability; and the coagulation system, leading to thromboembolism. Here we assembled a healthy human lung cell atlas meta-analysis with ~ 130,000 public single-cell transcriptomes and show that key elements of the bradykinin, angiotensin and coagulation systems are co-expressed with ACE2 in alveolar cells and associated with their differentiation dynamics, which could explain how changes in ACE2 promoted by SARS-CoV-2 cell entry result in the development of the three most severe clinical components of COVID-19.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Betacoronavirus / enzymology
  • Betacoronavirus / genetics*
  • Betacoronavirus / physiology
  • Blood Coagulation*
  • Gene Expression Profiling*
  • Humans
  • Kallikrein-Kinin System / genetics*
  • Peptidyl-Dipeptidase A / genetics*
  • Pulmonary Alveoli / cytology*
  • Pulmonary Alveoli / metabolism
  • Renin-Angiotensin System / genetics*
  • SARS-CoV-2
  • Serine Endopeptidases / genetics

Substances

  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2
  • Serine Endopeptidases
  • TMPRSS2 protein, human